Epidemiological evidence indicates that moderate alcohol consumption reduces the incidence of heart disease. Endothelial nitric oxide synthase (eNOS) is a key regulator of vascular homeostasis and ...myocardial functions through the controlled production of nitric oxide (*NO). These studies were conducted to determine if the apparent alcohol-associated cardioprotection is mediated, in part, through modulation of the eNOS protein and activity in the cardiovascular system. Rats were fed alcohol and eNOS protein and *NO production were evaluated at the end of 8 weeks. Myocardial and vascular function was assessed ex vivo in a subset of animals. Moderate alcohol improved postischemic myocardial systolic and diastolic function and attenuated the postischemic reduction in coronary vascular resistance. Moderate alcohol also enhanced maximum vascular relaxation by 26 +/- 0.2% and increased plasma *NO production concomitant with a greater than 2.5-fold increase in eNOS protein. Higher levels of alcohol impaired maximum vascular relaxation by 22 +/- 0.1%. These results suggest that moderate alcohol improves postischemic myocardial functions and increases *NO production by vascular endothelium. An increase in *NO may explain, at least in part, the cardioprotective benefits of moderate alcohol consumption.
The Surface Chemistry of Drilling Fluids Gray, George R; Caenn, Ryen; Darley, H. C. H
Composition and Properties of Drilling and Completion Fluids,
2011
Book Chapter
Summary
Focal dermal hypoplasia (Goltz) syndrome is a rare genetic disorder characterized by cutaneous, ectodermal and mesodermal defects. We present a case in which painful, exophytic granulation ...tissue has been the main symptom over the past 15 years. After unsatisfactory results with a number of treatment modalities including topical steroids, silver‐nitrate applications, cryotherapy, curettage, excision and pulsed‐dye laser, we achieved significant benefit with curettage in combination with photodynamic therapy. Although impaired wound healing has been described in focal dermal hypoplasia, this is, to our knowledge, the first time that pyogenic granuloma‐like lesions have been reported.
1 Wallace H. Coulter Department of Biomedical Engineering,
Georgia Institute of Technology and Emory University, Atlanta,
Georgia 30322; 2 Department of Pathology, Center for Free
Radical Biology, ...University of Alabama at Birmingham, Birmingham,
Alabama 35294; 3 Division of Pediatric Surgery, Department
of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
53226; and 4 Division of Cardiovascular Research, St.
Elizabeth's Medical Center and Tufts University School of
Medicine, Boston, Massachusetts 02135
Laminar shear stress activates c-Jun NH 2 -terminal
kinase (JNK) by the mechanisms involving both nitric oxide (NO) and
phosphatidylinositide 3-kinase (PI3K). Because protein kinase B
(Akt), a downstream effector of PI3K, has been shown to phosphorylate
and activate endothelial NO synthase, we hypothesized that Akt
regulates shear-dependent activation of JNK by stimulating NO
production. Here, we examined the role of Akt in shear-dependent NO
production and JNK activation by expressing a dominant negative Akt
mutant (Akt AA ) and a constitutively active mutant
(Akt Myr ) in bovine aortic endothelial cells (BAEC). As
expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin)
prevented shear-dependent stimulation of Akt and NO production.
Transient expression of Akt AA in BAEC by using a
recombinant adenoviral construct inhibited the shear-dependent
stimulation of NO production and JNK activation. However, transient
expression of Akt Myr by using a recombinant adenoviral
construct did not induce JNK activation. This is consistent with our
previous finding that NO is required, but not sufficient on its own, to
activate JNK in response to shear stress. These results and our
previous findings strongly suggest that shear stress triggers
activation of PI3K, Akt, and endothelial NO synthase, leading to
production of NO, which (along with O , which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt,
NO, and JNK by shear stress is likely to play a critical role in its
antiatherogenic effects.
endothelial cells; mitogen-activated protein kinase; atherosclerosis; endothelial nitric oxide synthase; mechanosensing
*
Y.-M. Go and Y. C. Boo contributed equally to this work.
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